The goal of this project is to obtain pharmacologically acceptable reagents that can modify sites on sickle cell hemoglobin to change its aggregating and gelling behavior. Exloratory experiments with aspirin have demonstrated that its acetyl group is transferred to sickle cell hemoglobin. However the extent of transacetylation is not large enough to decrease sickling adequately. Increass in acylating activity, and hence of antisickling effect, should be attainable by appropriate modification of either the leaving group, the salicylate, or of the acyl function. Several new classes of alternative aspirins, i.e. of modified acylsalicylates, will be synthesized to provide a series of mild reagents suitable for attaching a range of different side chains to sickle hemoglobin. These should modify the aggregation characteristics of HbS and sickling behavior in erythrocytes.